Analysis of exercise-induced changes in R wave amplitude in asymptomatic men with electrocardiographic ST-T changes at rest

Fifty asymptomatic men, 44 (88 percent) of whom were pilots or allied aviation personnel, were referred because of resting ST-T electrocardiographic changes indistinguishable from those of myocardial ischemia. Because of the nature of their occupations, cardiac catheterization was performed to establish the presence or absence of coronary artery disease. Exercise tests were performed and analyzed retrospectively with respect to exercise-induced changes in the S-T segment and R wave amplitude. The results were correlated with coronary angiographic and echocardiographic findings.The 50 subjects were classified into two groups: Group I, 5 men with angiographically proved coronary artery disease, and Group II, 45 men without significant coronary arterial obstruction. Analysis of the S-T segment changes at peak exercise showed 21 subjects (42 percent) with a positive exercise test and 29 (58 percent) with a negative test. All subjects in Group I had a positive test. Sixteen subjects (35 percent) in Group II had a false positive result. Analysis of exercise-induced changes in R wave amplitude revealed that six subjects had a positive R wave response on the basis of sum of the changes in voltage in the leads measured (Δ∑R). Four of the six subjects had coronary artery disease and the other two were thought to have a cardiomyopathy. One subject with coronary artery disease had a negative R wave response. Echocardiography revealed five subjects with asymmetric septal hypertrophy; two of these had a positive exercise test and three a negative test on the basis of S-T segment criteria.Thus, symptom-limited treadmill exercise testing of asymptomatic men with resting ST-T electrocardiographic changes produced a high incidence rate of false positive results when S-T segment criteria were used, whereas analysis of changes in R wave amplitude yielded only two false positive results, both in men who had evidence of other heart disease.     

Recognizing and improving patient nonadherence to statin therapy

Despite landmark trials demonstrating the benefits of statin therapy for lipid lowering and in the primary and secondary prevention of acute coronary events, many patients do not adhere to medication regimens. Although incremental gains have been made in lowering the absolute levels of total serum cholesterol in the general population, only one third of treated patients are achieving their lipid goals, with fewer than 20% of patients with cardiovascular disease at their target lipid goals. Only half of patients continue taking statins prescribed to them at 6 months, and only 30% to 40% continue taking them at 1 year. Predictors of poor adherence to statins are described, such as female gender and low socioeconomic status. Approaches that are physician focused and patient centered, such as frequent follow-up and serum lipid testing and better education of patients about cardiovascular disease, are suggested to offset a major impediment to achieving the full therapeutic outcomes promised by clinical trials.     

Orthodeoxia-platypnea due to intracardiac shunting relief with transcatheter double umbrella closure

The safety and efficacy of transcatheter clamshell occlusion of patent foramen ovale for relief of severe arterial desaturation and dyspnea in the upright position due to intracardiac shunting were examined in eight patients with excessive risk of surgical patent foramen ovale closure. All patients had successful reduction of intracardiac shunting with an immediate rise in oxygen saturation ?95% by implantation of a clamshell device on the atrial septum. Despite two early incidents of device embolization, retrieval and immediate re-implantation, and one patient with nonsustained atrial and ventricular arrhythmias, there were no adverse clinical sequelae. In follow-up evaluation transcatheter clamshell closure of patent foramen ovale has provided persistent relief from shuntrelated arterial desaturation and symptomatology in all living patients. © 1995 Wiley-Liss, Inc.     

Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion

The RF-amide peptides (RFRPs), including prolactin (PRL)-releasing peptide-31 (PrRP-31) and RFRP-1, have been reported to stimulate stress hormone secretion by either direct pituitary or indirect hypothalamic actions. We examined the possible direct effects of these peptides on PRL and adrenocorticotropin (adrenocorticotropic hormone [ACTH]) release from dispersed anterior pituitary cells in culture and on PRL and ACTH secretion following intracerebroventricular (icv) administration in vivo. Neither peptide significantly altered PRL or ACTH release from cultured pituitary cells (male rat donors). Central administration of 1.0 and 3.0 nmol of PrRP-31, but only the higher dose of RFRP-1, significantly elevated serum corticosterone levels in conscious male rats. The effect of PrRP-31 was not blocked by pretreatment (iv) with the corticotropin-releasing hormone (CRH) antagonist, α-helical CRH 9–41; however, pretreatment of the animals (iv) with an antiserum to CRH significantly lowered the hypothalamic-pituitary-adrenal axis response to central administration of PrRP-31. On the other hand, the release of PRL was significantly elevated by 3.0 nmol of RFRP-1, but not PrRP-31, in similarly treated, conscious male rats. Pretreatment with the catecholamine synthesis inhibitor, α-methyl-para-tyrosine, prevented the stimulation of PRL secretion observed following central administration of RFRP-1. RFRP-1 similarly did not alter PRL secretion in rats pretreated with the dopamine, D₂ receptor blocker, domperidone. These results suggest that the RF-amide peptides are not true neuroendocrine regulators of stress hormone secretion in the rat but, instead, act centrally to alter the release of neuroendocrine factors that do act in the pituitary gland to control PRL and ACTH release. In the case of RFRP-1, stimulation of PRL secretion is potentially owing to an action of the peptide to inhibit dopamine release into the median eminence. The corticosterone secretion observed following central administration of PrRP-31 does not appear, based on our current results, to be solely owing to an action of the peptide on CRH-producing neurons but, instead, may be a result of the ability of PrRP-31 to increase as well the exposure of the corticotrophs in vivo to other ACTH secretagogues, such as oxytocin or vasopressin.     

Cell distributions and functions of Toll-like receptor 4 studied by fluorescent gene constructs

Bacterial lipopolysaccharide (LPS) is recognized in mammals by a receptor complex composed of CD14, Toll-like receptor 4 (TLR4), and MD-2. The detailed mechanisms of how TLR4 transmits the signal from the outside to the inside of the cell remain to be elucidated. One way of studying TLR4 signaling mechanisms is to construct chimeras of TLR molecules C-terminally fused to fluorescent proteins and stably express these constructs in cells. Such constructs are functional when transfected into HEK293 epithelial cells. Confocal microscopy of TLR4 expression in live cells demonstrated pronounced expression on the plasma membrane as well in the Golgi apparatus. Studies were performed to clarify whether expression of TLR4 in the Golgi was necessary for LPS stimulation. Rapid recycling of TLR4/CD14/MD-2 complexes between the Golgi and the plasma membrane was a prominent phenomenon. In agreement with other types of plasma membrane receptors, aggregation of TLR4 by immobilized TLR4 antibodies was sufficient to induce signaling. Also, pharmacological disruption of the Golgi did not inhibit LPS induced NF-kappaB activation. Furthermore, LPS stimulation recruited the adapter molecule, MyD88, to the inside of the plasma membrane. Thus, LPS signaling commences on the plasma membrane and is independent of trafficking to the Golgi.